1. Field of the Invention
The invention relates to the field of physical, chemical and bio-sensing. More specifically, the invention relates to methods and systems for determining physical properties related to density, refractive index, composition of mixture or layer thickness of bio-related materials.
2. Description of the Related Art
Optical methods for determination parameters related to the refractive index properties of materials are well known. The most common optical techniques for bio-sensing and determining refractive index related properties of bio-related materials are surface plasmon resonance (SPR) and ellipsometry. The qualities of surface plasmon resonance (SPR) as well accepted direct detection technique for monitoring biological processes are described in more detail by Liedberg et al., in Sensors and Actuators, 4 (1983) 299-304. Ellipsometry often is used for analysing thin film properties as described by Hook et al. in Anal. Chem. 73 (2001) 5796-5804. Nevertheless, monitoring biochemical reactions in a liquid medium is less evident due to the varying environment through which the probing light beam has to propagate. A typical configuration for performing surface plasmon resonance measurements for liquid-phase sensing is the Kretschmann configuration, well known by a person skilled in the art. In this configuration, the laser generating the SPR evanescent wave is only propagating through the substrate, leading to a better control over the influence of the various buffer solutions used during a protein adsorption experiment.
For monitoring bound mass changes in liquid media, the use of various acoustic wave devices is well known and e.g. described by Gizeli in Biomolecular Sensors, Ed. E. Gizeli and C. R. Lowe (Taylor & Francis, London), 2002. Love mode devices are particular types of shear wave—surface acoustic wave devices using an overlayer with low shear wave velocity that helps trap the acoustic energy near the surface, thus increasing the sensitivity. The devices based on the propagation of a guided shear acoustic wave, present sensitivity improvements over the more usual quartz crystal microbalance as well as a compatibility with measurements in liquids.
Combined optical and acoustic measurements for material characterisation are described by Laschitsch A. et al. in Appl. Phys. Letters 77 (2000) 2252-2254. The document describes the combination of surface plasmon resonance spectroscopy and quartz crystal microweighing to determine the optical thickness and the acoustic thickness. By studying the ratio of the optical and the acoustical thickness, information related to the layer density is obtained which can be used for structural investigations and screening applications. Unfortunately, the method described in this document only allows to obtain density related information and not to obtain real values for the physical properties such as density, refractive index, layer thickness and possibly mixture composition.